The UCI Genomics High-Throughput Facility (GHTF) requests Shared Instrument Grant Support for a HiSeq 3000 next generation DNA sequencer to supplement and replace the current HiSeq 2500. The HiSeq 3000 is a state-of-the-art, DNA sequencer for biomedical research genomics and gene expression studies. This sequencer generates 750 Gbases of sequence in 3.5 days with an error rate of ~0.1%. The GHTF is the sole genomics research Core Facility for the UCI campus and Medical Center. Its mission is to make available to the research community emergent and current technologies that exceed the resources of the individual investigator. In addition to the UCI community, it offers services to regional companies and colleges that lack sequencing facilities. It has existed for sixteen years and flourished through several technological transformations by consistently offering high quality assistance in emerging technologies to the research community. In addition to Illumina DNA sequencing the GHTF offers PacBioRS long-range, single-molecule DNA sequencing, Affymetrix microarrays, Nanostring digital RNA counting, and Fluidigm C1 single cell fractionation. Illumina DNA sequencing with diversifying applications is growing rapidly and is currently the major research support offered by the GHTF. The HiSeq 3000 is capable of generating more than twice as much sequence per run as the current GHTF HiSeq 2500 v3 DNA sequencer, in about one-third of the time-at roughly the same cost. Acquisition of the sequencer is therefore essential to the GHTF. Currently the GHTF supports about fifty UCI investigators in all aspects of sample preparation and DNA and RNA sequence analysis including ChIP-, methyl-, RNA-, and DNA-seq. This application describes projects of twenty-seven biomedical researchers including investigations into diseased and normal tissue: melanoma, breast and colon cancer, Lou Gehrig's Disease, cardiomyopathy, alcoholism effect on liver function, drug addiction, and normal tissue morphogenesis and stem cell function, memory, skin regeneration, mitochondrial function, stem cell differentiation, DNA modification and neuronal plasticity, RNA splicing and polyadenylation. Most recently, the GHTF acquired the capability to perform DNA and RNA sequencing of single cells and is pursuing this technology and is working with investigators to develop new programs in understanding immune, skin and nervous systems at the level of the individual cell. The GHTF is the RNA sequencing center for the Neuro Library of Integrated Network-based Cellular Signatures (LINCS) program which is developing a complete cellular profile for Amyotrophic lateral sclerosis/Lou Gehrig's Disease. The GHTF provides technical seminars and workshops by commercial venders, workshops in bioinformatics for campus researchers, bioinformatics service support, and campus symposia. The HiSeq 3000 is a critical instrument in support of these GHTF functions.